Noonan syndrome and aortic coarctation

Abstract

Congenital heart defect (CHD) is present in half of the propositi with Noonan syndrome (NS). Aortic coarctation (AC) is rarely seen in NS, since only three male patients with NS and AC have been previously reported. On the other hand, AC is common in the Ull-rich-Turner syndrome, an aneuploidy disorder and not a mendelian syndrome. In order to evaluate if AC is truly rare in patients with NS, we reviewed our series of 184 propositi with NS and CHD. AC was diagnosed in 16 (8.7%) patients. There were 11 males and 5 females. All had normal chromosomes. Clinical characteristics of the patients are described. Familial occurrence was detected in one girl with NS and AC whose mother and sibs also had NS, but different form of CHDs. Thus, AC is more frequent in NS than previously reported.

Congenital heart defects in CTNNB1 syndrome: Raising clinical awareness

“…The combination of AVC defect and left-sided obstructions is rare in patients with Down syndrome, but described in patients with NS. 25 The present results support the inclusion of CTNNB1-NEDSDV among genetic syndromes associated with ToF, AVC defect, PV stenosis, and absent PV with IVS.…”

“…The defect is partial in our patient, associated with mild aortic arch hypoplasia. The combination of AVC defect and left‐sided obstructions is rare in patients with Down syndrome, but described in patients with NS 25 …”

Cardiac defects, morbidity and mortality in patients affected by RASopathies. CARNET study results

“…RASopathies are a group of disorders, caused by mutations in genes encoding for signal transducers of the RAS-MAPK cascade, affecting 1 in 1000-2500 children [1][2][3][4]. Among these disorders, Noonan syndrome (NS), NS with multiple lentigines (NSML, also known with the acronym LEOPARD syndrome), Costello syndrome (CS), and cardiofaciocutaneus syndrome (CFCS) share a similar systemic phenotype, with a wide spectrum of congenital heart disease (CHD) and hypertrophic cardiomyopathy (HCM) as major associated features [5][6][7][8][9][10]. Genotype-phenotype correlations have been established, including pulmonary stenosis (PS) and PTPN11 mutations, HCM and RAF1, HRAS and a subset of PTPN11 mutations, and mitral valve defects (MVD) and SHOC2 c.4A>G change [11][12][13][14][15].…”

The role of the protein tyrosine phosphatase SHP2 in cardiac development and disease

“…The most common cardiac manifestation in NS is pulmonic stenosis (PS) resulting from dysplastic valve leaflets, but stenosis of other valves (mitral valve), atrial septal defects (ASD), ventricular septal defects (VSD), atrioventricular septal defects (AVSD), or more rarely, double outlet right ventricle (DORV) also are seen [17, 18]. Hypertrophic cardiomyopathy (HCM) has also been reported in a few NS patients without SHP2 mutations [19], but genotype-phenotype correlation studies show that only 8% of SHP2 associated-NS patients present with this cardiac disorder [20, 21]. In contrast to NS, the majority of LS patients (~85–90%) develop HCM [22].…”